Gut Microbe-Derived Outer Membrane Vesicles: A Potential Platform to Control Cecal Load of Campylobacter jejuni

Acute diarrheal illness and gastroenteritis caused by Campylobacter jejuni infection remain significant public health risks in developing countries with substantial mortality and morbidity in humans, particularly in children under the age of five. Genetic diversities among Campylobacter jejuni and limited understanding of immunological correlations of host protection remain primary impediments for developing an effective measure to controlCampylobacter infection. Moreover, the lack of a reliable in vivo model to mimic natural infection against Campylobacter jejuni has substantially delayed the vaccine-development process. Given the role of bacterial outer membrane associated proteins in intestinal adherence and invasion as well as modulating dynamic interplay between host and pathogens, bacterial outer-membrane vesicles have emerged as a potential vaccine target against a number of gut pathogens, including Campylobacter jejuni. Here, we describe a mucosal vaccine strategy using chitosan-coated outer-membrane vesicles to induce specific immune responses against Campylobacter jejuni in mice. To overcome the challenges of mucosal delivery of outer membrane vesicles in terms of exposure to variable pH and risk of enzymatic degradation, we preferentially used chitosan as a nontoxic, mucoadhesive polymer. We show that intragastric delivery of chitosan-coated outer-membrane vesicles imparts significant immune protection against Campylobacter jejuni with high level local and systemic antibody production. Further, immunization with the outer membrane vesicles resulted in potent cellular responses with an increased CD4+ and CD8+ T cell population. Moreover, significant upregulation of IFN-γand IL-6 gene expression suggests that mucosal delivery of outer membrane vesicles promotes a Th1/Th2 mixed-type immune response. Together, as an acellular and nonreplicating canonical end product of bacterial secretion, mucosal delivery of outer membrane vesicles may represent a promising platform for developing an effective vaccine againstCampylobacter jejuni.